Preparation of intermediates



United States Patent l-[MONO- AND BIS(ALKANESULFONAMIDO) BEN- ZOYL] HYDRAZINE DERIVATIVES AND THE PREPARATION Aubrey A. Larsen, Schodack, N.Y., assignor to Sterling Drug Inc., New York, N.Y., a corporation of Delaware No Drawing. Filed Apr. 14, 1959, Ser. No. 806,235 23 Claims. (Cl. 260-601) This invention relates to new l-[monoand bis(alkanesulfonamido)benzoyl1hydrazines, l-[monoand bis(alkanesulfonamido)benzoyl]-2-lower-acylhydrazines, acidaddition salts thereof, and. to intermediates and processes used in their preparation.

A preferred aspect of the invention relates to compounds having the formula:

wherein Y represents a hydrogen atom or a lower-acyl radical, R represents an alkyl radical, R represents a hydrogen atom or a lower-alkyl radical, Q and Q each represents a hydrogen atom or a lower-alkyl, halogen (including fluorine, chlorine, bromine or iodine), hydroxy, lower-alkoxy, nitro, amino, lower-acylamino, lower-acyl, lower-acyloxy, cyano, lower-alkylmercapto, lower-alkylsulfinyl or lower-alkylsulfonyl radical, and n represents the integers 1 or 2. When two alkanesulfonamido groups are present, as is the case when n is 2, R can either represent the same or two dillerent alkane radicals and R can represent either the same or two different loweralkyl radicals or one R can be hydrogen and the other a lower-alkyl radical. When Q or Q represents the above-named radicals, they can be the same or difierent and can occupy any of the available positions on the benzene nucleus.

In the above general Formula I, Y represents a hydrogen atom or a lower-acyl radical. The lower-acyl radical can contain from one to about five carbon atoms and can be either straight or branched and can, in addition, bear one or more further substituents on the ot-carbon atom such as halogen (for example chlorine or bromine), amino and cyano. Thus Y includes such groups, inter alia, as formyl, acetyl, propionyl, n-butyryl, isobutyryl, n-valeryl, a-chloroacetyl, ma-dichloroacetyl, a,oc,a-trichloroacetyl, a-aminoacetyl, a-cyanoacetyl, and a-chloroisobutyryl.

In the above general Formula I, R represents an alkyl radical. It can contain from one to about twenty carbon atoms and can be either straight or branched. Thus R includes such groups, inter alia, as methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, pentyl, hexyl, heptyl, octyl, decyl, dodecyl and eicosyl.

In the above general Formula I, R represents a hydrogen atom or a lower-alkyl radical. The lower-alkyl radical can contain from one to about four carbon atoms and can be either straight or branched. R thus includes such groups, inter alia, as methyl, ethyl, n-propyl, isopropyl, n-butyl and isobutyl.

The N(R)SO R group or groups in the above general Formula I can occupy any of the available positions in the benzene ring, although when n is 2, it is preferred that these groups occupy the 3 and 5 positions with respect to the -CONHNH- group.

In the above general Formula I, Q and Q each represent a hydrogen atom, or a lower-alkyl, halogen, hydroxy,

Patented Mar. 10, 1964 lower-alkoxy, nitro, amino, lower-acylamino, lower-acyl, lower-acyloxy, cyano, lower-alkylmercapto, lower-alkylsulfinyl and lower-alkylsulfonyl radical. When Q or Q represents a lower-alkyl, lower-alkoxy, lower-acylamino, lower-acyl, lower-acyloxy, lower-alkylmercapto, loweralkylsulfinyl or lower-alkylsulfonyl radical, the radicals can contain from one to about five carbon atoms and can be either straight or branched. Furthermore, when Q or Q represents a lower-acylamino or lower-acyloxy radical, the lower-acyl moiety can be further substituted by one or more further substituents on the u-carbon atom such as halogen (for example chlorine or bromine) or cyano radicals. Thus Q and Q each include such radicals, inter alia, as methoxy, S-methylbutoxy, acetylamino, isobutyrylamino, acetyl, propionyl, acetoxy, propionoxy, methylmercapto, isopropylmercapto, methylsulfinyl, methylsulfonyl, isopropylsulfinyl, isopropylsulfonyl, a-chloroacetylamino, a-cyanoacetylamino, a-chloroacetoxy and ot-cyanoacetoxy radicals.

The compounds of the invention wherein Y is hydrogen are prepared by reacting hydrazine with a lower-alkyl monoor bis(alkanesulfonamido)benzoate ester having the formula:

wherein R, R, Q, Q, and n have the meanings given above and R represents a lower-alkyl group containing from one to about four carbon atoms. A preferred method comprises reacting a lower-alkyl monoor bis- (alkanesulfonamido)benzoate ester of Formula II with hydrazine hydrate at a temperature between about 40 C. and about 200 C. Although it is preferred to use 100% hydrazine hydrate, any commercially available grade of aqueous hydrazine hydrate such as an aqueous solution can also be used. The reaction can be carried out in the absence of any solvent or, if desired, it may be conducted in an organic solvent inert under the conditions of the reaction. Suitable solvents for the purpose are methanol, ethanol, 2-propanol, ethylene glycol, diethylene glycol and the like.

The compounds of Formula I wherein R is a loweralkyl radical are prepared by reacting a lower-alkyl monoor bis(N-lower-alkylalkanesulfonamido)benzoate ester with hydrazine using the reaction conditions described above.

The compounds of Formula I wherein Y is a loweracyl radical are prepared from the corresponding compounds wherein Y is H by reacting the latter with an acylating agent which, on reaction, provides an acyl radical containing from one to about five carbon atoms. A preferred method comprises reacting the l-[monoand bis(loWer-alkanesulfonamido)benzoyl]hydrazines of Formula I with a member of the group consisting of lower-acyl anhydrides, lower-acyl halides and lower-acyl lower-alkyl carbonates at a temperature between about 10 C. and about C. The reaction can be effected with or without the use of an acid-acceptor if desired.

1? carbonate, sodium acetate, triethylamine, ide and the like.

The compounds of Formula II, which are useful as intermediates in the preparation of compounds of Formula I, are prepared by reacting the corresponding loweralkyl monoor diaminobenzoate ester with an alkanesulfonyl halide. A preferred method comprises reacting the lower-alkyl aminobenzoate ester with the alkanesulfonyl halide at a temperature in the range from about C. to about 100 C. and in the presence of an acidacceptor. The reaction may be carried out without the use of a solvent or, if desired, in an organic solvent inert under the conditions of the reaction. Suitable solvents for the purpose are benzene, acetone, ethyl acetate, chloroform, ethylene dichloride and the like. The purpose of the acid-acceptor is to. take up the hydrogen halide which is split out during the course of the reaction. The acidacceptor is a basic substance which forms water-soluble byproducts easily separable from the main product of the reaction, and includes such substances as pyridine, triethylamine, sodium hydroxide and the like. The acidacceptor can also be in the form of an excess quantity of the lower-alkyl monoor diaminobenzoate ester.

The compounds of Formula II wherein R is loweralkyl are prepared by reacting a lower-alkyl monoor bis(alkanesulfonamido)benzoate ester in the presence of an acid-acceptor with a lower-alkylating agent, for example a lower-alkyl sulfate, a lower-alkyl halide or a lower-alkyl p-toluenesulfonate. Preferred lower-alkylating agents are lower-alkyl sulfates. When a loWer-alkyl sulfate is used, the reaction is preferably carried out at a temperature in the range from about 0 C. to about 50 C. in an aqueous medium although water-miscible solvents such as methanol and ethanol can be used as well. The purpose of the acid-acceptor is to take up the lower-alkyl acid sulfate or the sulfuric acid produced in the reaction and includes such substances as sodium hydroxide, potassium hydroxide and the like.

In the compounds of Formula I, where two alkanesulfonamido groups are present, as is the case where n is 2, R can either represent the same or two different alkane radicals and R can represent either the same or two different lower-alkyl radicals or one R can be hydrogen and the other a lower-alkyl radical. The 1-[bis(alkanesulfonamido)benzoyl1hydrazines where the two R and/ or R groups are different are prepared by reacting a lower-alkyl nitro-mono (lower-alkanesulfonamido benzoate ester of Formula II (Q is N0 Q is H; n is 1) with a lower-alkylating agent, for example a lower-alkyl sulfate, as described above. The resulting lower-alkyl nitromono(N lower alkylalkanesulfonamido)benzoate esters are then reduced to the corresponding lower-alkyl aminomono( N lower alkylalkanesulfonamido)benzoate esters using any of the conventional methods for the chemical reduction of an aromatic nitro group to the amino group, for example, iron and hydrochloric acid, tin and hydrochloric acid, zinc and aqueous alcohol, ferrous sulfate and ammonia or ammonium sulfide in aqueous alcohol.

The resulting lower-alkyl amino-mono(N-lower-alkylalkanesulfonamido)benzoate esters can then be reacted with an alkanesulfonyl halide as described above to introduce a second and, if desired, different alkanesulfonamido group. The resulting lower-alkyl alkanesulfonarnido-(N- lower-alkylalkanesulfonamido)benzoate esters can, if desired, be alkylated again with a second, different loweralkylating agent thus producing the lower-alkyl bis(N- lower-alkyla1kanesulfonamido)benzoate esters. Reaction of the latter with hydrazine as described above affords the 1 [bis (N-lower-alkylalkanesulfonamido benzoyl] hydra- Zines of Formula I where the two R and R groups in the two alkanesulfonamido groups are different.

The above-described procedure can be used to prepare compounds of Formula I where n is 2 and where the two R and R groups in the two alkanesulfonamido groups are either the same or different. A second method for presodium hydroxparing the compounds where the alkanesulfonamido groups are the same comprises reducing a lower-alkyl dinitrobenzoate ester with hydrogen over a platinum or palladium-on-charcoal catalyst. The resulting loweralkyl diaminobenzoate esters are then reacted with two molar equivalents of an alkanesulfonyl halide to produce the corresponding lower-alkyl bis(alkanesulfonamido)benzoate esters. The latter can either be reacted with two molar equivalents of a lower-alkylating agent to produce the lower-alkyl bis(N-lower-alkylalkanesulfonamido)benzoate esters or with hydrazine to produce compounds of Formula I wherein R is H and n is 2.

The acid-addition salts of the compounds of Formula I are water-soluble and are the form in which the compounds are conveniently prepared for use physiologically. Therapeutically acceptable salts are salts whose anions are innocuous to the animal organism in effective doses of the salts, so that beneficial physiological properties inherent in the free bases are not vitiated by side-effects ascribable to the anions; in other words, the latter do not substantially affect the physiological properties inherent in the cations. Appropriate acid-addition salts are those derived from mineral acids such as hydrochloric acid, hydrobromic acid, hydriodic acid, nitric acid, sulfuric acid and phosphoric acid, and organic acids such as acetic acid, citric acid, lactic acid, tartaric acid and quinic acid.

The acid-addition salts are prepared either by dissolving the free base in an aqueous solution containing the appropriate acid and isolating the salt by evaporating the solution; or by reacting the free base and acid in an organic solvent, in which case the salt separates directly or can be obtained by concentration of the solution.

Although therapeutically acceptable salts are preferred, those having toxic anions are also useful. All acidaddition salts are useful as intermediates in purification of the free bases, and toxic acid-addition salts are also useful as intermediates in preparing therapeutically acceptable salts by ion exchange procedures.

The compounds of Formula I have been found to possess bactericidal activity against such organisms as Staphylococcus aurezts, Ebert/tells: typhi, Pseudomonas aeruginosa, Diplacoccus pneimzoniac, Clostrz'a'ium welchii, Mycobacterium tuberculosis, and the like; and amoebicidal activity against Endamoeba criceti.

The bactericidal activity was determined in vitro by measuring the minimal concentration necessary to kill the bacteria in ten minutes, and it was found that the compounds were eifective in dilutions ranging from 1:1000 to 1:13,000. They were effective either when dissolved in acid solutions, such as aqueous acetic, propionic, quinic or phthalic acids, or when dispersed in neutral aqueous medium by means of a surface active agent.

When used as surface antibacterial agents the compounds of the invention are prepared for use by dissolving a salt form in an aqueous medium containing a surfactant and applied to a surface to be disinfected by conventional means such as spraying, swabbing, immersion and the like. In such cases when the compounds are to be used externally, toxic acid-addition salts can be used.

The amoebicidal activity was determined in vivo in hamsters by finding the oral dose which, when administered orally to a group of hamsters every day for four days, would clear all the animals in that group of the organism.

When used as amoebicidal agents, the compounds are prepared for oral use by incorporating them in tablet or capsule form or in a non-toxic carrier to be administered as a syrup.

The LD of the compounds as determined by toxicity studies in mice is of the order of magnitude of 2000 mg./kg. orally and from 200 to 1000 mg./kg. intravenously. LD is defined as the dose fatal to fifty percent of the animals tested at the particular dose level.

The structures of the compounds of the invention have been established by chemical analysis and by the processes for their preparation, which can only lead to compounds of the assigned structure.

The following examples will further illustrate the invention without the latter being limited thereto.

PREPARATION OF INTERMEDIATES Example 1 Ethyl 2-methanesulf0namidobenzoate (II; R is CH R is H, R" is C H 1118 1, Q and Q are H).

Sixty-six grams (0.4 mole) of ethyl anthranilate were dissolved in a solution of 200 ml. of benzene and 50 ml. of pyridine. To the solution was added 34 ml. (52 g., 0.4 mole) of methanesulfonyl chloride over a ten minute period. The reaction mixture was cooled slightly and then warmed on a steam bath for several minutes. After cooling to 15 C., the insoluble material was filtered OE and the filtrate taken to dryness. The residual solid was taken into aqueous sodium hydroxide, the solution was filtered, and the filtrate was acidified with dilute hydrochloric acid. The precipitated solid was collected and air-dried giving 75 g. of crude product, M.P. 9798 C. (uncorr.). A g. sample was recrystallized from 2-propanol to give 10 g. of ethyl 2-methanesulfonamidobenzoate, M.P. 93.595.7 C. (corr.).

Analysis.Calcd. for C H NO S: N, 5.76; S, 13.17. Found: N, 5.65; S, 13.44.

Example 2 Ethyl 2-methanesalf0namid0-4-nitr0benzoate (II; R is CH R is H, R is C H n is 1, Q is 4-NO Q is H) was prepared from 71 g. (0.34 mole) of ethyl 2-amino-4- nitrobenzoate and 29 ml. (43 g., 0.41 mole) of methanesulfonyl chloride in 31 ml. of pyridine and 330 ml. of acetone according to the manipulative procedure described above in Example 1. The crude product was recrystallized twice from methanol to give 15 g. of ethyl 2-methanesulfonamide 4 nitrobenzoate, M.P. 1535-15 6.3 C. (corr.).

Analysis.Calcd. for C H N O S: N, 4.86; S, 11.12. Found: N, 4.91; S, 11.62.

Example 3 Ethyl 5-chloro-2-methanesalfonamia'obenzoate (II; R is CH R is H, R" is C I-I n is 1, Q is 5-Cl, Q is H) was prepared from 45 g. (0.225 mole) of ethyl 2-amino-5- chlorobenzoate and 30 ml. (44 g., 0.43 mole) of methanesulfonyl chloride in 50 ml. of pyridine and 200 ml. of benzene according to the manipulative procedure described above in Example 1. The crude product was re-esterified in absolute ethanol saturated with hydrogen chloride gas and recrystallized from ethanol and washed with dilute sodium bicarbonate solution to give 9 g. of ethyl 5-chloro 2 methanesulfonamidobenzoate, M.P. 109.4111.0 C. (corr.).

Analysis.-Calcd. for C H ClNO S: N, 5.04; S, 11.54. Found: N, 5.15; S, 11.60.

Example 4 Ethyl Z-butanesalfonamidobenzoate (II; R is R is H, R C H n is 1, Q and Q are H) was prepared from 72.5 g. (0.44 mole) of ethyl anthranilate and 31 ml. (36 g., 0.23 mole) of butanesulfonyl chloride according to the manipulative procedure described above in Example 1. The product was purified by dissolving it in dilute sodium hydroxide and reprecipitating it by acidification with dilute hydrochloric acid. There was thus obtained 8 g. of ethyl Z-butanesulfonamidobenzoate, M.P. 35.5-40.1 C. (corr.).

Analysis.-Calcd. for C H NO S: N, 4.91; S, 11.50. Found: N, 4.92; S, 11.24.

Example 5 Ethyl 3-methanesulf0namidobenzoate (II; R is CH R is H, R" is CH n is 1, Q and Q are was prepared from 65 g. (0.39 mole) of ethyl 3-aminobenzoate and 35 ml. (52 g., 0.45 mole) of methanesulfonyl chloride in 50 ml. of pyridine and 200 ml. of benzene according to the manipulative procedure described above in Example 1. The crude product was purified by precipitation from an acidified solution in dilute alkali giving 49 g. of product. A 20 g. sample was recrystallized from 2-propanol to give 18 g. of ethyl 3-methanesulfonamidobenzoate, M.P. 118-119 C. (uncorr.).

Analysis.Calcd. for C I-I NO S: N, 5.76; S, 13.18. Found: N, 5.83; S, 12.74.

Example 6 Ethyl 3-methanesulfonamido-5-nitrobenz0ate (II; R is CH R is H, R" is C H n is 1, Q is 5-NO Q is H) was prepared from 67 g. (0.32 mole) of ethyl 3-amino-5 nitrobenzoate and 27 ml. (40 g., 0.35 mole) of methanesulfonyl chloride in 28 ml. of pyridine and 300 ml. of acetone according to the manipulative procedure described above in Example 1. The product was recrystallized from methanol to give 10 g. of ethyl 3-methanesulfonarnido-5- nitrobenzoate, M.P. 177.9178.7 C. (corr.).

Analysis.Calcd. for C H N O S: N.E. (Neutral Equivalent), 288; N, 4.86. Found: N.E., 287; N, 4.88.

Example 7 Ethyl S-butanesulfonamidobenzoate (II; R is R is H, R is C H n is 1, Q and Q are H) was prepared from 63 g. (0.38 mole) of ethyl 3-aminobenzoate and 48 ml. (55.7 g., 0.37 mole) of butanesulfonyl chloride in 50 ml. of pyridine and 200 ml. of benzene according to the manipulative procedure described above in Example 1. The crude product was recrystallized from methanol to give 60 g. of ethyl 3-butanesulfonamidobenzoate, M.P. 5256 C. (corr.).

Example 8 Example 9 Ethyl 3-acet0xy-5-butanesulfonamidobenzoate (II; R is CH (CH R is H, R is C H n is 1, Q is 3-CH COO, Q is H) Was prepared by dissolving 25.2 g. (0.1 mole) of ethyl 3-acetoxy-5-nitrobenzoate in ml. of ethyl acetate and reducing over a platinum catalyst under fifty pounds of hydrogen. When reduction was complete, the catalyst Was removed by filtration. The filtrate was added to a cold solution of 17.3 g. (0.11 mole) of butanesulfonyl chloride and 25 ml. of pyridine. The mixture was allowed to stand in a refrigerator for about fifteen hours and at room temperature for forty-eight hours. The reaction mixture was concentrated to a small volume and the residue poured into Water. The precipitated solid was collected, dried and recrystallized twice from Z-propanol giving 14.5 g. of ethyl 3-acetoxy-S-sulfonamidobenzoate, M.P. 119.0l20.8 C. (corr.).

Analysis.Calcd. for C H NO S: N, 4.08; S, 9.34. Found: N, 4.08; S, 9.19.

Example 10 Methyl Z-acetoxy-S-butanesulfonamidobenzoate (II; R

is CH (CH R is H, R" is CH n is 1, Q is 2-CH COO,

Q is H) was prepared from 23.9 g. (0.1 mole) of methyl 2-acetoxy-S-nitrobenzoate in 150ml. of ethyl acetate and 17.3 g. (0.11 mole) of butanesulfonyl chloride in 25 ml. of pyridine according to the manipulative procedure described above in Example 9. The product was. recrystallized from benzene giving 14 g. of methyl 2- acetoxy-5-butanesulfonamidobenzoate, M.P. 82.8-84.8 C. (corr.).

Analysis.-Calcd. for C I-1 N N, 4.25; S, 9.73. Found: N, 4.22; S, 9.77.

Example 1] Ethyl 4-methanesulfonamidobenzoate (II; R is CH R is H, R" is C H n is 1, and Q and Q are H) was prepared from 165 g. (1.0 mole) of ethyl 4-aminobenzoate and 57.3 g. (0.5 mole) of methanesulfonyl chloride in 500 ml. of benzene according to the manipulative procedure described above in Example 1. The crude product was recrystallized from 2-propanol giving 49.6 g. of ethyl 4- methanesulfonamidobenzoate, M.P. 129.8131.7 C. (corr.).

Analysis.Calcd. for G i-1 N0 8: N, 5.76; S, 13.18. Found: N, 5.82; S, 12.80.

Example 12 Ethyl 4-ethanesulf0namid0benzoate (II; R is C H R is H, R is C H n is 1, Q and Q are H) was prepared from 16.5 g. (0.1 mole) of ethyl 4-aminobenzoate and 14.3 g. 0.11 mole) of ethanesulfonyl chloride in 125 ml. of pyridine according to the manipulative procedure described above in Example 1. The crude product was recrystallized from 2-propanol giving 18.5 g. of ethyl 4- ethanesulfonamidobenzoate, M.P. 157-159 C. (uncorr.).

Example 13 Ethyl 4-pr0panesulfonamid0benzoate (II; R is R is H, R" is C H n is 1, Q and Q are H), was reppared from 23.1 g. (0.4 mole) of ethyl 4-aminobenzoate and 21.4 g. 0.15 mole) of propanesulfonyl chloride in 125 ml. of pyridine according to the manipulative procedure described above in Example 1. The crude prodnot was purified by dissolving it in dilute sodium hydroxide and reprecipitating by acidifying with dilute hydrochloric acid. There was thus obtained 36 g. of ethyl 4-propanesulfonamidobenzoate, M.P. 122-127.5 C. (uncorr.).

Example 14 Ethyl 4-(2-pr0panesulfonamid0)benzoate (II; R is (CH CH R is H, R is C H n is 1, Q and Q are H) was prepared from 28.2 g. (0.17 mole) of ethyl 4-aminobenzoate and 24.3 g. (0.17 mole) of 2-propanesulfonyl chloride in 110 ml. of pyridine according to the manipulative procedure described above in Example 1. The product was recrystallized from ethanol giving 9.0 g. of ethyl 4-(2- propanesulfonamido)benzoate, M.P. 145-147 C. (un corr.).

Example 15 Ethyl 4-butanesulfonamidobenzoate (II; R is R is H, R" is C H n is 1, Q and Q are H) was prepared from 74 g. (0.45 mole) of ethyl 4-arninobenzoate and 70 g. (0.45 mole) of butanesulfonyl chloride in 50 ml. of pyridine and 350 ml. of benzene according to the manipulative procedure described above in Example 1. The product was recrystallized from methanol giving 32 g. of ethyl 4-butanesulfonamidobenzoate, M.P. 78.9-87 C. (corr.).

Analysis.Calcd. for C I-1 N0 5: N, 4.91; S, 11.24. Found: N, 5.01; S, 11.10.

Example 16 Methyl 4-butanesulfonamido-Z-chlorobenzoate (II; R is CH (CH R is H, R is CH n is 1, Q is 2-Cl, Q is H) was prepared from 20 g. (0.108 mole) of methyl '4-amino-2-chlorobenzoate and 19.5 g. (0.124 mole) of butanesulfonyl chloride in 150 ml. of pyridine according to the manipulative procedure described above in Example 1. The product was recrystallized Once from a benzene-ligroin (Skelly B) mixture and once from methanol to give 18.5 g. of methyl 4-butanesulfonamido-2- chlorobenzoate, M.P. 75.6-78.4" C. (corr.).

Analysis.-Calcd. for C I-I ClNO S: N. 4.58; S, 10.48. Found: N, 4.50; S, 10.46.

Example 17 Ethyl 2-acet0xy-4-butanesulfonamidobenzoate (II; R is CH (CH R is H, R" is C H n is 1, Q is 2-CH COO, Q is H) was prepared from 25.4 g. (0.1 mole) of ethyl 2-acetoxy-4-nitrobenzoate in 120 ml. of ethyl acetate and 17.5 g. (0.11 mole) of butanesulfonyl chloride in 125 ml. of pyridine according to the manipulative procedure described above in Example 9. The product was recrystallized from methanol to give 24.5 g. of ethyl 2-acetoxy-4- butanesulfonamidobenzote, M.P. -87 C. (uncorr.).

Example 18 Ethyl 4-butanesulfonamido-Z-methoxybenzoate (II; R is CH (CH R is H, R is C H n is 1, Q is 2-CH O, Q is H) was prepared from 7.5 g. (0.038 mole) of ethyl 4-amino-2-methoxybenzoate and 13.5 g. (0.08 mole) of butanesulfonyl chloride in 125 ml. of pyridine according to the manipulative procedure described above in Example 1. The crude product was purified by dissolving it in aqueous sodium hydroxide and reprecipitating it by acidifying with dilute hydrochloric acid. There was thus obtained 9.6 g. of ethyl 4-butanesulfonamido-Z-methoxybenzoate, M.P. 103-105 C. (uncorr.).

Example 1 9 Methyl 4-butanesalf0namid0-3-hydr0xybenzoate (II; R is CH (CH R is H, R is CH n is 1, Q is 3-HO, Q is H) was prepared from 13 g. (0.066 mole) of methyl 3-hydroxy-4-nitrobenzoate in 250 ml. of ethyl acetate and 9.5 g. (0.061 mole) of butanesulfonyl chloride in 25 ml. of pyridine according to the manipulative procedure described above in Example 9. The product was purified by dissolving it in dilute aqueous sodium hydroxide and reprecipitating it by acidifying with dilute hydrochloric acid. There was thus obtained 10.3 g. of methyl 4-butanesulfonamido-3-hydroxybenzoate, M.P. 124-128 C. (uncorr.).

S ilnalysis-Calcd. for C H NO S: S, 11.19. Found:

Example 20 Ethyl 4-pentanesulf0namidobenzoate (II; R is R is H, R is C H n is 1, Q and Q are H) was prepared from 16.5 g. (0.1 mole) of ethyl 4-aminobenzoate and 18.8 g. (0.11 mole) of pentanesulfonyl chloride in ml. of pyridine according to the manipulative procedure described above in Example 1. The crude prodnot was recrystallized from dilute methanol giving 21.1 g. of ethyl 4-pentanesulforramidobenzoate, M.P. 78-83" C (uncorr.).

Example 21 Ethyl 4-hexanesulf0namidobenzoate (II; R is R is H, R" is C H n is 1, Q and Q are H) was prepared from 8.3 g. (0.05 mole) of ethyl 4-aminobenzoate and 10 .4 g. (0.056 mole) of hexanesulronyl chloride in 75 ml. of pyridine according to the manipulative procedure described above in Example 1. The crude product was recrystallized from dilute methanol to give 12.4 g. of ethyl 4-hexanesulfonamidobenzoate, M.P. 65-70" C. (uncorr.).

Example 22 Ethyl 4-heptanesulfonamidobenzoate (II; R is R is H, R" is C H n is 1, Q and Q are H) was prepared from 15.8 g. (0.096 mole) of ethyl 4-aminobenzoate and 21.0 g. (0.107 mole) of heptanesulfonyl chloride in 125 ml. of pyridine. The crude product was purified by dissolving it in dilute aqueous sodium hydroxide and reprecipitating it by acidifying with dilute hydrochloric acid. There was thus obtained 33.3 g. of ethyl 4-heptanesulfonamidobenzoate, M.P. 72.5-76 C. (uncorr.).

Example 23 Ethyl 4decanesulf0namid0benzoate (II; R is R is H, R" is C H n is 1, Q and Q are H) was prepared from 5.3 g. (0.032 mole) of ethyl 4-aminobenzoate and 8.0 g. (0.033 mole) of decanesulfonyl chloride in '75 ml. of pyridine according to the manipulative procedure described above in Example 1. The crude product was recrystallized from methanol to give 6.7 g. of ethyl 4- decanesulfonamidobenzoate, M.P. 86-89 C. (uncorr.).

Example 24 Methyl 4-acetyl-2-butanesulfonamidobenzoate (II; R is CH (CH R is H, R is CH n is 1, Q is 4-CH CO, Q is H).

By reducing methyl 4-acetyl-2-nitrobenzoate [Mayer et al., Ber. 65B, 1333 (1932)] with hydrogen over a platinum catalyst according to the manipulative procedure described above in Example 9, and subsequent treatment of the methyl 4-acetyl-2-aminobenzoate produced with a molar equivalent amount of butanesulfonyl chloride and a molar excess of pyridine, there can be obtained methyl 4-acetyl-2-butanesulfonamidobenzoate.

Example 25 Ethyl 3-butanesulfonamido-ti-methylmercaptobenzoate (II; R is CH (CH R is H, R" is C H n is 1, Q is 6-CH S, Q is H).

By treatment of ethyl 2-chloro-5-nitrobenzoate [Kenner et al., J. Chem. Soc. 119, 1053 (1921)] with methyl mercaptan in the presence of an acid-acceptor, there can be obtained ethyl Z-methylmercapto-5-nitrobenzoate which on treatment with ammonium sulfide in an appropriate organic solvent, for example ethanol, would afford ethyl 3-amino-6-methylmercapt0benzoate. On treatment of the latter with a molar equivalent amount of butanesulfonyl chloride in the presence of pyridine according to the manipulative procedure described above in Example 1, there can be obtained ethyl 3-butanesulfonamido-6- methylmercaptobenzoate.

Example 26 Ethyl 3-butanesulf0namido-6 methylsulfinylbenzoate (II; R is CH (CH R is H, R is C H n is 1, Q is 6-CH SO, Q is H).

By dissolving the ethyl Z-methylmercapto-S-nitrobenzoate obtained above in Example 25 in an appropriate organic solvent such as ethanol and treating the solution with one molar equivalent of peracetic acid (hydrogen peroxide dissolved in glacial acetic acid), there can be obtained ethyl Z-methylsulfinyl-S-nitrobenzoate which on reduction with ammonium sulfide in an appropriate organic solvent, for example ethanol, alfords ethyl 3-amino- 10 Example 27 Ethyl 3 butanesulfonamido-fi-methylsulfonylbenzaate (II; R is CH (CH R is H, R is C H n is 1, Q is 6-CH SO Q is H).

By dissolving the ethyl Z-methylmercapto-S-nitrobenzoate obtained above in Example 25 in an appropriate organic solvent such as ethanol and treating the solution with two molar equivalents of peracetic acid (hydrogen peroxide dissolved in glacial acetic acid), there can be obtained ethyl 2-methylsulfonyl-5-nitr0benzoate which on reduction with ammonium sulfide in an appropriate organic solvent, for example ethanol, afi'ords ethyl 3-amino- 6-methylsulfonylbenzoate. On treatment of the latter compound with one molar equivalent amount of butanesulfonyl chloride in the presence of pyridine according to the manipulative procedure described above in Example 1, there can be obtained ethyl 3-butanesulfonamido-6- methylsulfonylbenzoate.

Example 28 Ethyl 3-butanesulf0namid0-6-cyan0benz0ate (II; R is CH (CH R is H, R is C H n is 1, Q is 6-CN, Q is H).

By reacting ethyl 2-chloro-5-nitrobenzoate with sodium cyanide in an appropriate organic solvent such as ethanol, acetone or acetonitrile, and then adding a catalytic amount of sodium iodide to facilitate the reaction, there can be obtained ethyl 2-cyano-5-nitrobenzoate which on reduction with ammonium sulfide in an appropriate organic solvent, for example ethanol, would afford ethyl 3- amino-6-cyanobenzoate. On treatment of the latter with butanesulfonyl chloride in the presence of pyridine according to the manipulative procedure described above in Example 1, there can be obtained ethyl 3-butanesulfonamido-6-cyanobenzoate.

Example 29 Example 30 Ethyl 3,5-bis(methanesulfonamido)benzoate (II; R is CH R is H, R is C H n is 2, Q and Q are H) was prepared from 24 g. (0.1 mole) of ethyl 3,5-dinitrobenzoate in ml. of ethyl acetate, 25.9 g. (0.22 mole) of methanesulfonyl chloride and 18 ml. of pyridine according to the manipulative procedure described above in Example 9. The crude product was recrystallized from 2-propanol giving 12 g. of ethyl 3,5-bis(methanesulfonamido)benzoate, M.P. 245.8248.0 C. (corn).

Analysis.Calcd. for C11H15N2O5S2 N, 8 S, 19.05- Found: N, 8.11; S, 18.90.

Example 31 Ethyl 3,5-bz's(butanesulfonamido)benzoate (II; R is CH (CH R is H, R" is C H n is 2, Q and Q are H) was prepared from 24.0 g. (0.1 mole) of ethyl 3,5- dinitrobenzoate in 125 ml. of ethyl acetate, 34.6 g. (0.22 mole) of butanesulfonyl chloride and 18 ml. of pyridine according to the manipulative procedure described above in Example 9. The crude product was recrystallized from ethanol giving 18 g. of ethyl 3,5-bis(butanesulfonamido) benzoate, M.P. l77.2l77.8 C. (corn).

Analysis.Calcd. for C H N O S N, 6.67; S, 15.24; N.E., 420.5. Found: N, 6.54; S, 15.59; NE, 407.

Example 32 Ethyl 3 bulanesalfonamido 5 methanesalfonamidobenzoate (II; R is CH and CH (CH R is H, n is 2, Q and Q are H).

By reducing the ethyl 3-methanesulfonamido-S-nitrobenzoate obtained above in Example 6 with ammonium sulfide in an appropriate organic solvent, for example ethanol, there can be obtained ethyl 3-amino-5-methanesulfonamidobenzoate. On reaction of the latter with one molar equivalent amount of butanesulfonyl chloride in the presence of a molar excess of pyridine, there can be obtained ethyl 3-butanesulfonamido-5-methanesulfonamidobenzoate.

Example 33 Ethyl 4-(N-methylbutanesulfonamido) benzoate (II; R is CH (CH R is CH R" is C H n is 1, Q and Q are H Ethyl 4-butanesulfonamido benzoate (13.6 g., 0.05 mole) was dissolved in 200 ml. of an aqueous solution containing 2.0 g. (0.05 mole) of sodium hydroxide. To the solution was added 7.57 g. (0.06 mole) of methyl sulfate. The mixture was stirred for two and a half hours while adding additional amounts of dilute sodium hydroxide to maintain an alkaline medium. The supernatant liquid was then decanted from the gummy material that had separated, and the gum was washed once with water by decantation and then dissolved in ether. The ethereal solution was extracted with four 100 ml. portions of water. The ether layer was dried and the solvent distilled off leaving 12.2 g. of ethyl 4-(N-methylbutanesulfonamido) benzoate as a yellow-orange viscous liquid.

Example 34 Ethyl 3 butanesulfonamido 5 (N isobutylmethanesalfnamid0)benzoate (II; R is CH (CH R is H and (CH CHCH R is C H n is 2, Q and Q are H).

By reacting the ethyl 3-methanesulfonamido-S-nitrobenzoate obtained above in Example 6 with isobutylsulfate and sodium hydroxide according to the manipulative procedure described above in Example 33, there can be obtained ethyl 3-(N-isobutylmethanesulfonamido)-5-nitrobenzoate. By reducing the latter with ammonium sulfide in an appropriate organic solvent, for example ethanol, there can be obtained ethyl 3-amino-5-(N-isobutylmethanesulfonamido)benzoate. On reaction of the latter with one molar equivalent amount of butanesulfonyl chloride in the presence of a molar excess of pyridine, there can be obtained ethyl 3-butanesulfonamido-5-(N-isobutylmethanesulfonamido)benzoate.

Example 35 Ethyl 3 batanesulfonamido 6 methoxy 5 methylbenzoate (II; R is CH (CH R is H, R is C H n is 1, Q is 5-CH Q is 6-CH O).

By reducing ethyl 2-methoxy-3-methyl-5-nitrobenzoate with hydrogen over a platinum catalyst according to the manipulative procedure described above in Example 9, there can be obtained ethyl 3-amino-6-methoxy-5-methylbenzoate. By reacting the latter with a molar equivalent amount of butanesulfonyl chloride in the presence of a molar excess of pyridine according to the manipulative procedure described above in Example 1, there can be obtained ethyl 3-butanesulfonamido-6-methoxy 5 methylbenzoate.

FINAL PRODUCTS Example 36 (3-methanesalf0namidobenzoyl)hydrazine (I; R is CH R is H, n is 1, Y, Q, and Q are H).

Ethyl 2-methanesulfonamidobenzoate (17.5 g., 0.071 mole) was dissolved in 150 ml. of absolute ethanol and 20 ml. of hydrazine hydrate was added. The reaction mixture was refluxed for about forty hours and then concentrated on a steam bath toabout one third of its volume.

The reaction mixture was then cooled and acidified with acetic acid. On scratching and cooling, the product separated and was collected by filtration and recrystallized from ethanol to give 8.1 g. of (Z-methanesulfonamidobenzoyl)hydrazine, M.P. 13l.4-132.8 C. (corr.).

Analysis.Calcd. for C H N O S: N.E., 229.2; N, 18.32. Found: N.E. 227.7; N, 18.80.

(2-methanesulfonamidobenzoyl)hydrazine was found to be bacteriostatic at a dilution of 1:10,000 when tested in vitro against Staph. aureus and E. T yphi.

(2-methanesulfonamidobenzoyl)hydrazine can be reacted with hydrochloric acid, hydrobromic acid, hydriodic acid, nitric acid, sulfuric acid, phosphoric acid, acetic acid, citric acid, lactic acid, tartaric acid or quinic acid to give the hydrochloride, hydrobromide, hydriodide, nitrate, sulface (or bisulfate), phosphate (or acid phosphate), acetate, citrate (or acid citrate), lactate, tartrate (or bitartrate) or quinate salts, respectively.

Example 37 (2-methanesalfonamid0-4-nitr0benz0yl hydrazine (I; R is CH R is H, n is 1, Y is H, Q is 4-NO Q is H).

By reacting the ethyl Z-methanesulfonamido-4-nitrobenzoate obtained above in Example 2 with hydrazine hydrate according to the manipulative procedure described above in Example 36, there can be obtained (Z-methancsulfonamido-4-nitrobenzoyl)hydrazine.

Example 38 (5-chl0ro-2-methanesalfonamidobenzoyl)hydrazine (1; R is CH R is H, n is 1, Yis H, Q is 5-Cl, Q' is H).

' By reacting the ethyl 5-chloro-2-methanesulfonamidobenzoate obtained above in Example 3 with hydrazine hydrate according to the manipulative procedure described above in Example 36, there can be obtained (5-chloro-2 methanesulfonamidobenzoyl)hydrazine.

Example 39 (2-batanesalfonamidobenzoyl hydrazine (I; R is R is H, n is 1, Y, Q, and Q are H) was prepared from 9.5 g. (0.033 mole) of ethyl Z-butanesulfonamidobenzoate and 30 ml. of hydrazine hydrate in 30 ml. of methanol according to the manipulative procedure described above in Example 36. The product was purified by reprecipitation from its solution in dilute alkali. There was thus obtained 8.0 g. of (Z-butanesulfonamidobenzozyl)hydrazine, M.P. 106.3107.9 C. (corr.).

Analysis.Calcd. for C11H17N3O3SI N, 15.45; S, 11.81. Found: N, 15.31; S, 11.83.

(2-butanesulfonamidobenzoyl)hydrazine can be reacted with hydrochloric acid to give the hydrochloride salt.

Example 40 Example 41 (3-methanesulfonamido-S-nitrobenzoyl) hydrazine (I; R is CH R is H, n is 1, Y is H, Q is S NO Q is H) was prepared from 28.8 g. (0.1 mole) of ethyl 3-methanesulfonamido-5-nitrobenzoate and 20 g. of hydrazine hydrate in 200 ml. of absolute ethanol according to the manipulative procedure described above in Example 36.

The product was recrystallized from boiling water to give 12 g. of (3-methanesulfonamido-S-nitrobenzoyl)hydrazine, M.P. 2498-2505" C. (corn).

Analysis.Calcd. for C H N O S: N 5.10; N, 20.43. Found: N 5.38; N, 20.17.

(3-methanesulfonamido 5 nitrobenzoyl)hydrazine can be reacted with hydrochloric acid to give the hydrochloride salt.

Example 42 (3-amino-5-methanesulfonamidobenzoyl)hydrazine dihydrochloride (I; R is CH R is H, n is 1, Y is H, Q is 3-NH Q is H).

Eighteen grams (0.065 mole) of (S-methanesulfonamido-5-nitrobenzoyl)hydrazine, obtained above in Example 40, were dissolved in 200 ml. of water and ml. of hydrazine hydrate. About 0.2 gram of Raney nickel catalyst was added and the reaction mixture was warmed on a steam bath to about 35 C. Warming was continued until foaming stopped, and the reaction mixture was then filtered from the catalyst and the filtrate acidified with dilute acid. The filtrate was concentrated in vacuo to a volume of about 40 ml. On chilling, the product separated as a gray-pink solid. It was collected and recrystallized once from ethanol and then converted to the hydrochloride salt with concentrated hydrochloric acid. The salt was recrystallized from a 2-propanol-water mixture giving 3 g. of (3-amino-5-methanesulfonamido benzoyl)- hydrazine dihydrochloride, M.P. 241.1-243.2 C. (corn).

Analysis.-Calcd. for C I-I N O S2HCl: N, 17.65; Cl, 22.35. Found: N, 17.30; Cl, 22.15.

Example 43 Example 44 (3-batanesulfonamido-S-nitr0benz0yl)hydrazine (I; R is CH (CH R is H, n is 1, Y is H, Q is 5-NO Q is {11).

By reacting the ethyl 3-butanesulfonamido-S-nitrobenzoate, obtained above in Example 8, with hydrazine hydrate according to the manipulative procedure described above in Example 36, there can be obtained (B-butanesulfonamido-S-nitrobenzoyl)hydrazine.

Example 45 (5-amin0-3-butanesulfonamidobenzoyl)hydrazine (I; R is CH (CH R is H, n is 1, Yis H, Q is S-NH Q is H). By reacting the (3 butanesulfonamido-S-nitrobenzoyl)- hydrazine obtained above in Example 44 with hydrazine hydrate in the presence of Raney nickel catalyst according to the manipulative procedure described above in Example 42, there can be obtained (5-amino-3-butanesulfonamidobenzoyl) hydrazine.

Example 46 (3-butanesulfonamid0-5-hydr0xy benzoyl hydrazine (I; R is CH (CH R is H, n is 1, Y is H, Q is S-HO, Q is H) was prepared from 14 g. (0.041 mole) of ethyl 3- acetoxy-S-butanesulfonamidobenzoate and 25 ml. of hydrazine hydrate in 25 m1. of ethanol. The product was recrystallized from 2-propanol giving 4 g. of (3-butanesulfonamido-S-hydroxybenzoyl)hydrazine, M.P. 166.4- 169.0 C. (corn).

Analysis.Calcd. for C H N O S: N, 14.62; S, 11.16. Found: N, 14.40; S, 11.23.

(3-butanesulfonamido 5 hydroxybenzoyl)hydrazine can be reacted with hydrochloric acid to give the hydrochloride salt.

Example 47 (5-butanesulfonamido-Z-hydroxybenzoyl)hydrazine (I; R is CH (CH R is H, n is 1, Y is H, Q is 2-HO, Q is H) was prepared from 17 g. (0.052 mole) of methyl 2-acetoxy-5-butanesulfonamidobenzoate and 35 ml. of hydrazine hydrate in 35 ml. of absolute ethanol according to the manipulative procedure described above in Example 36. The product was recrystallized from ethanol giving 8.0 g. of (5-butanesulfonamido-2-hydroxybenzoyl)- hydrazine, M.P. 140.2141.6 C. (corn).

A nalysis.--Calcd. for C H N O S: N, 14.62; S, 11.16. Found: N, 14.42; S, 11.24.

(S-butanesulfonamido 2 hydroxybenzoyl)hydrazine can be reacted with hydrochloric acid to give the hydrochloride salt.

(S-butanesulfonamido 2 hydroxybenzoyl)hydrazine was found to be bacteriostatic at a dilution of 121,000 when tested in vitro against Staph. aareus and E. typhi. In amoebiasis studies in hamsters, it cleared two out of five animals of the organism, Endamoeba criceti, at a dose level of mg./ kg. day. Intravenous toxicity studies in mice have shown the LD to be 170 i 10 mg./kg.

Example 48 (4-methanesulfonamidobenzoyl)hydrazine (I; R is CH R is H, n is 1, Y, Q, and Q are H) was prepared from 20 g. (0.082 mole) of ethyl 4-methanesulfonamidobenzoate and 20 ml. of hydrazine hydrate in ml. of ethanol according to the manipulative procedure described above in Example 36. The crude product was recrystallized twice from ethanol giving 7.5 g. of (4- methanesulfonamidobenzoyl)hydrazine, M.P. 230.7- 233.9 C. (corn).

Analysis.--Calcd. for C H N O S: N.E., 229; N, 18.32. Found: N.E., 234; N, 18.50.

(4-methanesulfonamidobenzoyl)hydrazine can be reacted with hydrochloric acid to give the hydrochloride salt.

Example 49 (4-ethanesulfonamidobenzoyl) hydrazine (I; R is C H R is H, n is 1, Y, Q, and Q are H) was prepared'from 18.5 g. (0.072 mole) of ethyl 4-ethanesulfonamidobenzoate and 25 ml. of hydrazine hydrate according to the manipulative procedure described above in Example 36. The product was recrystallized from 2-propanol giving 6 g. of (4-ethanesulfonamidobenzoyl)hydrazine, M.P. 205.2- 208.2 C. (corn).

Analysis.Calcd. for C H N O S: N, 17.28; S, 13.18. Found: N, 17.15; S, 12.78.

(4-ethanesulfonamidobenzoyl)hydrazine can be reacted with hydrochloric acid to give the hydrochloride salt.

(4-ethanesulfonamidobenzoyl)hydrazine was found to be bacteriostatic at a dilution of 1:1,000 when tested in vitro against Staph. aureus and E. typhi. In vivo studies in mice showed that a dose of 300 mg./kg./day was effective to cure eight mice out of a [group of ten infected with D. pneamoniae. I-n amoebiasis studies in hamsters, it cleared one out of five animals of the organism, Endamoeba criceti, at a dose level of 100 mg./l g./day.

. Example 50 (4-pr0panesulfonamidobenzoyl)hydrazine (I; R is R is H, n is 1, Y, Q, and Q are H) was prepared from 36 g. (0.132 mole) of ethyl 4-propanesulfonamidobenzoate and 40 ml. of hydrazine hydrate in 200 ml. of etha- 1101 according to the manipulative procedure described above in Example 36. The product was recrystallized from dilute ethanol giving 11.8 g. of (4-propanesulf0n- 15 amidobenzoyl)hydrazine, M.P. 195.2196.6 C. (corr.).

Analysis.Calcd.1fr CH15N303SI S, N, 16-33. Found: S; 12.31; N, 16.23;

-(4-propanesul'fonamidobenzoyl)hydrazine can be reacted with hydrochloric acid to give the hydrochloride salt.

(4-propanesulfonamidobenzoyl)hydrazine was found to be bacteriostatic at a dilution of 1:1,000 when tested in vitro against Staph. aureus. In vivo studies in mice showed that a dose of 40 n1g./kg./ day was effective to cure nine mice out of a group of ten infected with type I D. pneumomae.

Example 51 [4-(2-propanesulfonamido)benzoyl]hydrazine (I; R is (CH CH, R is H, n is 1, Y, Q, and Q are H) was prepared from 9.0 g. (0.033 mole) of ethyl 4-(2-propanesulfonamido)benzoate and a molar excess of hydrazine hydrate in ethanol according to the manipulative procedure described above in Example 36. The product was recrystallized from dilute methanol giving 7.4 g. of [4- (2-propanesulfonamido)benzoyl1hydrazine, M.P. 245.4- 250.2 C. (corr.).

Analysis.Calcd. for C H N O S: N, 16.33; S, 12.46. Found: N, 16.30; S, 12.39.

[4-(2-propanesulfonamido)benzoyl]hydrazine can be reacted with hydrochloric acid to give the hydrochloride salt.

In vivo studies in mice showedthat a dose of 450 mg./ kg./day was effective to cure all animals in a group of ten infected with type I D. pneumoniae.

Example 52 (4-batanesulfonamidobenzoyl) hydrazine (I; R is R is H, n is 1, Y, Q, and Q are H) was prepared from 15 g. (0.053 mole) of ethyl 4-butanesulfonamidobenzoate and 45 ml. of hydrazine hydrate in 45 ml. of methanol according to the manipulative procedure described above in Example 36. The product was recrystallized from methanol giving 4-butanesulfonamidobenzoyl hydrazine, M.P. 189.7-191.0 C. (corr.).

Analysis.Ca1cd. for C11H17H3O3SZ NE, 271; N, 15.49. Found: NE, 273; N, 15.59.

(4 butanesulfonamidobenzoyl)hydrazine can be reacted with hydrochloric acid to give the hydrochloride salt.

'(4-butanesulfonamidobenzoyl)hydrazine was found to be baoteriostatic at a dilution of 1:1,000 when tested in vitro against Staph. aureus, E. typhi and types I, II and III D. pneumoniae. In vivo studies in mice showed that a dose of 400 mg./kg./ day was effective to cure all mice in a group of ten infected with type I D. pneamoniae. The oral LD as revealed'by toxicity studies in mice has been shown to be around 2000 mg./kg.

Example 53 *(4-butanesulfonamid0-Z-chl0robenzoyl)hydrazine (I; R is CH (CH R is H, n. is 1, Y is H, Q is 2-Cl, Q is H) was prepared from g. (0.066 mole) of methyl 4-butanesuilfonamido-2-chlorobenzoate and 50 ml. of hydrazine in 50 ml. of methanol according to the manipulative procedure described above in Example 36. The product was recrystallized from ethanol giving 12.3 g. of (4-butanesulfonamido-Z-chlorobenzoyl)hydrazine, M.P. 153.2155.2 C. (corr.).

Analysis.-Calcd. f or C H ClN O S: N, 13.74; S, 10.48. Found: N, 13.63; S, 10.53.

Example 54 (4-butanesulfonamido-Z-hydr0xybenzoyl)hydrazine (I; R is CH (CH R is H, n is 1, Y is H, Q is Z-HO, Q is H) was prepared [from 24 g. (0.07 mole) of ethyl 2- acetoxy-4 butanesulfonamidobenzoate and 60 ml. of hydrazine hydrate in 60 ml. of absolute ethanol according to the manipulative procedure described above in Example 36. The product was recrystallized from dimethyl-- formamide giving 9.5 g. of (4-butanesulfonamido-2-hydroxybenzoyDhydrazine, M.P. 257.0258.4 C. (corr.).

Analysis.-Calcd. fOI' C11H17N304SI N, S, Found: N, 14.89; S, 11.38.

(4-butanesulfonamido-Z-hydroxybenzoyl)hydrazine can be reacted with hydrochloric acid to give the hydrochloride salt.

Example 55 (4-bmanesulfonamiaio-Z-methoxybenzoyl)hydrazine I; R is CH (CH R is H, n is 1, Y is H, Q is 2-CH O, Q is H) was prepared from 9.6 g. (0.032 mole) of ethyl 4- butanesulfonamido-Z-methoxybenzoate and 40 ml. of hydrazine hydrate in ml. of ethanol according to the manipulative procedure described above in Example 36. The product was recrystallized from ethanol giving 5.5 g. of (4 butanesulfonamido-2 methoxybenzoyl)hydrazine, M.P. 230.0232.6 C. (corr.).

Analysis.Calcd. -for C H N O S: N, 13.94; S, 10.63 Found: N, 14.08; S, 10.56.

(4 butanesulfonamido 2 methoxybenzoyl)hydrazine can be reacted with hydrochloric acid to give the hydrochloride salt.

Example 56 (4-bwtanesulfonamido-3-hydroxybenzoyl)hydrazine (I; R is CH -(CH R is H, n is 1, Y is H, Q is 3-HO, Q is H) was prepared from 10 g. (0.035 mole) of methyl 4-butanes-ulfonamido-3-hydroxybenzoate and 20 ml. of hydrazine hydrate in 20 ml. of ethanol according to the manipulative procedure described above in Example 36. The product was recrystallized from methanol giving 6.2 g. of (4-butanesulfonamido-3-hydroxybenzoyl)hydrazine, M.P. 222.6-224.0 C. (corr.).

Analysis.--Calcd. for C H N O S: N, 14.62; S, 11.16. Found: N, 14.90; S, 10.93.

(4 butanes-ulfonamido 3 hydroxybenzoyl)hydra zine can be reacted with hydrochloric acid to give the hydrochloride salt.

(4 butanesuifonamido 3 hydroxybenzoyl)hydrazine was found to be bacteriostatic at a dilution of 1:1,000 when tested in vitro against Staph. aureus, E. typhi, Pseud. aeruginosa and Cl. welchii; It was bactericidal against H37Rv strain Myeo. tuberculosis at a dilution of 1:13,000.

Example 57 (4-pentanesalfonamidobenzoyl)hydrazine (I; R is R is H, n is 1, Y, Q, and Q are H) Was prepared from 21.3 g. (0.0712 mole) of ethyl 4-pentanesulfonamidobenzoate and 55 ml. (1.1 mole) of hydrazine hydrate in 200 ml. of ethanol according to the manipulative procedure described above in Example 36. The product was recrystallized from dilute methanol giving 5.8 g. of (4-pentanesulfonamidobenzoyl(hydrazine, M. P. 191.4- 192 6 C. (corr.).

(4-pentanesulfonamidobenzoyl)hydrazine can -be reacted with hydrochloric acid to give the hydrochloride salt.

(4-pentanesulfonamidobenzoyl)hydrazine was found to be bacteriostatic at a dilution of 1:1,000 when tested in vitro against Staph. aureus and E. typlzi. In vivo studies in mice showed that a dose of 400 mg./kg./day was effective to cure all mice in a group of ten infected with D. pneamoniae. Against type I D. pneumaniae there were eight survivors out of a group of ten when medicated at a dose level of 450 mg./kg./day of the compound.

Example 58 (4-hexanesulfonamidobenzoyl) hydrazine (I; R is CH (CH R is H, n is 1, Y, Q, and Q are H) was prepared from 12.4 g. (0.04 mole) of ethyl 4-hexanesulfonamidobenzoate and 35 ml. of hydrazine hydrate in 75 m1. of ethanol according to the manipulative procedure described above in Example 36. The product was recrystallized from methanol giving 8.8 g. of l-hexanesulfonamidobenzoyl)hydrazine, M.P. 186.4-188.8 C. (corr.).

Analysis.Calcd. for C H N O S: N, 14.03; S, 10.70. Found: N, 13.93; S, 11.00.

(4-hexanesulfonamidobenzoyl)hydrazine can be reacted with hydrochloric acid to give the hydrochloride sa t.

(,4-hexanesulfonamidobenzoyl)hydrazine was found to be bacteriostatic at a dilution of 1:10,000 when tested in vitro against Staph. aureus and E. typhi.

Example 59 4-(heptanesulfonamidobenzoyl)hydrazine (I; R is CH (CH R is H, n is 1, Y, Q, and Q areH) was prepared from 24.7 g. (0.075 mole) of ethyl 4-heptanesulfonamidobenzoate according to the manipulative procedure described above in Example 36. The product was recrystallized from methanol giving 13.4 g. of (4-heptanesulfonamidobenzoyl)hydrazine, M.P. l91.0193.6 C. (corr.).

Analysis.Calcd. for C H N O S; N, 13.41; C, 10.23. Found: N, 13.33; S. 9.86.

(4-heptanesulfonamidobenzoyl)hydrazine can be reacted with hydrochloric acid to' give the hydrochloride salt.

(4-heptanesulfonamidobenzoyl)hydrazine was found to be bacteriostatic at a dilution of 1:10,000 when tested in Vitro against Staph. aureus and E. typhz'.

Example 60 (4 -decansalfonamidobenzoyl)hydrazine (I; R is CH (CI-I R is H, n is 1, Y, Q, and Q are H) was prepared from 6.7 g. (0.018 mole) of ethyl 4-decanesulfonamidobenzoate and a molar excess of hydrazine hydrate according to the manipulative procedure described above in Example 36. The product was recrystallized from methanol giving 5.2 g. of (4-decanesulfonamidobenzoy1)hydrazine, M.P. 1868-1888 C. (corr.). Analysis.Ca1cd. for C H N O S: N, 11.82; S, 9.02. Found: N, 11.60; S, 8.77.

(4-decanesulfonamidobenzoyl)hydrazine can be reacted with hydrochloric acid to give the hydrochloride salt.

Example 61 (4 acetyl-Z-butanesulfonamialobenzoyl) hydrazine (I; R is CH (CH R is H, n is 1, Y is H, Q is 4-CH CO, Q is H).

By reacting methyl 4-acetyl-2-butanesulfonamidobenzoate obtained above in Example 24 with a molar excess of hydrazine hydrate in an appropriate organic solvent, for example methanol, according to the manipulative procedure described above in Example 36, there can be obtained (4-acetyl-2-butanesulfonamidobenzoyl)hydrazine.

Example 62 (3 batanesulfonamid0-6-methylmercaptobenzoyl)hydrazine (I; R is CH (CH R is H, n is 1, Y is H, Q is 6-CI-I S, Q is H).

By reacting the ethyl 3-butanesulfonamido-6-methylmercaptobenzoate prepared above in Example 25 with a molar excess of hydrazine hydrate according to the manipulative procedure described above in Example 36, there can be obtained (3-butanesulfonamido-6-methylmercaptobenzoyl)hydrazine.

Example 63 (S-butanesulfonamido 6 methylsalfinylbenzoyl)hydrazine (I; R is CH (CH R is H, n is 1, Y is H, Q is 6-CH SO, Q is H).

By reacting the ethyl 3-bntanesulfonamido-6-methylsulfinylbenzoate prepared above in Example 26 with a molar excess of hydrazine hydrate according to the manipulative procedure described above in Example 36,

there can be obtained (3-butanesulfonarnido-6-methylsulfinylbenzoyl) hydrazine.

Example 64 (3-butanesulf0namid0 6 methylsalfonylbenzoyl)hydrazine (I; R is CH (CH R is H, n is 1, Y is H, Q is 6-CH SO Q is H).

By reacting the ethyl 3-butanesulfonarnido-6-methylsulfonylbenzoate obtained above in Example 27 with a molar excess of hydrazine hydrate according to the manipulative procedure described above in Example 36, there can be obtained (3-butanesulfonamido-6-methylsulfonylbenzoyl) hydrazine.

Example 65 (3-butanesulfonamid0 6 cyanobenzoyl)hydrazine (I; R is CH (CH R is H, n is 1, Y is H, Q is 6CN, Q is H).

By reacting the ethyl 3-butanesulfonamido-6-cyanobenzoate obtained above in Example 28 with a molar excess of hydrazine hydrate according to the manipulative procedure described above in Example 36, there can be obtained (3 butanesulfonamido-6-cyano benzoyl)-hydrazine.

Example 66 (Z-butanesulfonamido 4 isopropylbenzoyl)hydrazine [I; R is CH (CH R is H, n is 1, Y is H, Q is 4-CH(CH Q is H].

By reacting the methyl 2-butanesulfonamidol-isopropylbenzoate prepared above in Example 29 with a molar excess of hydrazine hydrate according to the manipulative procedure described above in Example 36, there can be obtained (Z-butanesulfonamido-4-isopropylbenzoyl) hydrazine.

Example 67 [3,5 bis(methanesulf0namid0)benz0yl]hydrazine (I; R is CH R is H, n is 2, Y, Q, and Q are H) was prepared from 45 g. (0.13 mole) of ethyl 3,5-bis(methane sulfonamido)benzoate and 100 ml. of hydrazine hydrate in 100 ml. of methanol according to the manipulative procedure described above in Example 36. The product was recrystallized from a dimethylformarnide-ethanol mixture giving 19 g. of [3,5-bis (methanesulfonamido)benzoyl]hydrazine, M.P. 254.8258.4 C. (corr.).

Analysis.Calcd. for C H N O S N, 17.38; S, 19.89. Found: N, 17.47; S, 19.32.

I [3,5 bis(methanesulfonamido)benzoyl1hydrazine can be reacted with hydrochloric acid to give the hydrochloride salt.

Example 68 [3,5 bis(butanesulf0namid0)benzoylflzydrazine (I; R is CH (CH R is H, n is 2, Y, Q, and Q are H) was prepared from 29 g. (0.07 mole) of ethyl 3,5-bis (butanesulfonamido)benzoate and 55 ml. of hydrazine hydrate in 50 ml. of ethanol according to the manipulative procedure described above in Example 36. The product was recrystallized from ethanol giving 16 g. of [3,5- bis(butanesulfonarnido)benzoyl]hydrazine, MP. 231.0235.4 C. (corr.).

Analysis.-Calcd. for C H N O S N, 13.78; S, 15.78. Found: N, 13.67; 5, 15.75.

[3,5-bis(butanesulfonarnido)benzoyl]hydrazine can be reacted with hydrochloric acid to give the hydrochloride salt.

Example 69 (S-butanesalfonamido 5 methanesulfonamidobenzoyl)hydrazine (I; R is CH and CH (CH R is H, n

1 9 Example 70 [4 (N methylbutanesulfonamido)benzoyl] hydrazine (I; R is CH (CH R is CH n is 1, Y, Q, and Q are H) was prepared from 12.2 g. (0.043 mole) of ethyl 4-(N-methylbutanesulfonamido)benzoate and 25 m1. of hydrazine hydrate in 100 ml. of ethanol according to the manipulative procedure described above in Example 36. The product was recrystallized from dilute methanol giving 2.6 g. of [4-(N-methylbutanesulfonamido)benzoyl]hydrazine.

Analysis.Calcd. for C H N O S: S, 11.23; N, 14.72. Found: S, 11.20; N, 14.50.

[4 (N methylbutanesulfonamido)benzoylJhydrazine can be reacted with hydrochloric acid to give the hydrochloride salt.

In vivo studies in mice showed that a dose of 300 mg./kg./day of [4- N-methylbutanesulfonamido benzoyl]hydrazine was eifective to cure seven mice out of a group of ten infected with D. pneamoniae, and a dose of 225 mg./kg./day was effective to cure five mice out of a group of ten infected with type I D. pneumoniae. In amoebiasis studies in hamsters, it cleared all animals in a group of three of the organism, Endamoeba criceti, at a dose level of 100 mg./kg./day.

Example 71 [3-batanesulfonamid0 5 (N-isobatylmetlzanesulfonamia'o)benzoyflhydrazine (I; R is CH and CH (CH R is H and (CH CHCH n is 2, Y, Q, and Q are H).

By reacting the ethyl 3-butanesulfonamido-5-(N-isobutylmethanesulfonamido)benzoate obtained above in Example 34 with a molar excess of hydrazine hydrate according to the manipulative procedure described above in Example 36, there can be obtained [3-butanesulfonamido- 5-(N-isobutylmethanesulfonarnido)benzoylJhydrazine.

['3-butanesulfonamido 5 (N-isobutylmethanesulfonamido)benzoyl]hydrazine can be reacted with hydrochloric acid, hydrobromic acid, hydriodic acid, nitric acid, sulfuric acid, phosphoric acid, acetic acid, citric acid, lactic acid, tartaric acid, or quinic acid to give the hydrochloride, hydrobromide, hydriodide, nitrate, sulfate (or bisulfate), phosphate (or acid phosphate), acetate, citrate (or acid citrate), lactate, tartrate (or bitartrate) or quinate salts, respectively.

Example 72 (S-butanesalfonamido 6 methxy-5-methylbenz0yl)- hydrazine (I; R is CH (CH R is H, n is 1, Y is H, Q is -CH Q is 6-CH O).

By reacting the ethyl 3-butanesulfonamido-6-methoxy- S-methylbenzoate obtainedabove in Example 35 with a molar excess of hydrazine hydrate according to the manipulative procedure described above in Example 36, there can be obtained (3-butanesulfonamido-6-methoxy- 5 -methylb enzoyl) hydrazine.

Example 73 1 -acetyl-2-(4-batanesalfonamidobenzoyl) hydrazine (I; R is CH (CH R is H, n is 1, Y is CH CO, Q and Q are H).

A mixture of (4-butanesulfonamidobenzoyl)hydrazine (13.6 g., 0.05 mole) and 50 ml. of acetic anhydride was heated briefly on a steam bath until all the solid had dissolved. The reaction mixture was allowed to stand at room temperature for about hours, and the precipitated solid which had separated was then collected by filtration and washed thoroughly with petroleum ether (Skelly B). There was thus obtained 13.1 g. of l-acetyl- 2-(4-butanesulfonamidobenzoyl)hydrazine, M.P. 145.6- 146.6 C. (corn).

Analysis.Calcd. for C H N O S: N, 13.41; S 10.23. Found: N, 13.05; S, 10.50.

In vivo studies in mice showed that a dose of 450 mg./kg./day of 1-acetyl-2-(4-butanesulfonamidobenzoyl)hydrazine was efiective to cure five mice out of a group of ten infected with type I D.pneum0niae. Intravenous toxicity studies in mice have shown the ALD to be 1000 mg./kg.

Example 74 I-dichloroacetyl 2 (4-batanesalfonamidobenzoyl)hydrazine (I; R is CH (CH R is H, n is 1, Y is Cl CHCO, Q and Q are H).

Ten grams (0.037 mole) of (4-butanesulfonamidobenzoyl)hydrazine were dissolved in 35 ml. of dimethylformamide. To the solution was added 6.0 g. (0.041 mole) of dichloroacetyl chloride. The reaction mixture, which had warmed to 76 C., was cooled briefly to room temperature and then heated on a steam bath for five hours. The reaction mixture was poured onto crushed ice with stirring, and the sticky mass which separated solidified on scratching. The solid was collected by filtration and recrystallized from dilute dimethylformamide giving 8.5 g. of 1-dichloroacetyl-2-(4-butanesulfonamidobenzoyl)hydrazine, M.P. 198.4-202.6 C. (corn).

Analysis.-Calcd. for C H CI N O S: Cl, 18.55; N, 10.99. Found: Cl, 18.37; N, 11.04.

The oral ALD of 1-dichloroacetyl-2-(4-butanesulfonamidobenzoyDhydrazine as determined by toxicity studies in mice has beenshown to be greater than 2000 mg./kg.

Example 75 I aminoacezyl 2 (4-butanesalf0namidobenzoyl)hydrazine hydrobromide (I; R is CH (CH R is H, n is 1, Y is NH CH CO, Q and Q are H).

A solution of 21 g. (0.1 mole) of carbobenzoxyglycine in 14 ml. of triethylamine was cooled with stirring to -10 to 20 C. To the stirred solution was added a solution of 14 ml. of isobutyl chlorocarbonate in 25 ml. of acetone over a ten minute period. (4-butanesulfonamidobenzoyl)hydrazine (23.5 g., 0.087 mole) was added all at once. The reaction mixture was stirred two hours at room temperature and then allowed to stand for about fifteen hours. To the reaction mixture was added 600 ml. of hot water with stirring. The solid which had separated was collected, washed with water and recrystallized from methanol giving 20 g. of l-carbobenzoxyaminoacetyl-2-(4 butanesulfonamidobenzoyl)hydrazine, M.P. 234-236 C. (corn).

Analysis.Calcd. for C H N O S: N, 12.12. Found: N, 11.76.

A sample of the above product (19.5 g.) was treated with 70 ml. of 30% hydrobromic acid in glacial acetic acid. The reaction mass was diluted with ether and the solid collected by filtration. The product was recrystallized from methanol giving 13 g. of 1-aminoacetyl-2- (4-butanesulfonamidobenzoyl)hydrazine hydrobromide, M.P. 274.0-275.2 C. (corn).

Analysis.-Calcd. for C H N O S.HBr: Br, 19.53; N, 13.69. Found: Br, 19.27; N, 13.75.

In vivo studies in mice showed that a dose of 400 mg./ kg./day of 1-arninoacetyl-2-(4-butanesu-lfonamidobenzoyl)hydrazine hydrobromide was eifective to cure nine mice out of a group of ten infected with D. pneamonfae. In amoebiasis studies in hamsters, it cleared two out of five animals of the organism, Endamoeba criceti, at a dose level of mg./kg./day.

l-arninoacetyl 2 (4-butanesulfonamidobenzoyl)hydrazine can be reacted with hydrochloric acid, hydriodic acid, nitric acid, sulfuric acid, phosphoric acid, acetic acid, citric acid, lactic acid, tartaric acid, or quinic acid to give the hydrochloride, hydriodide, nitrate, sulfate (or bisulfate), phosphate (or acid phosphate), acetate, citrate (or acid citrate), lactate, tartrate (or bitartrate) or quinate sa'lts, respectively.

Example 76 1-acetyl-2-(3-acet0xy 5 butanesulfonamidobenzoyl) hydrazine (I; R is OH (CI-I n is 1, Y is CH CO, Q is 3-CH COO, Q is H).

By reacting the (3-butanesulfonamido-S-hydroxybem 21 zoyl)hydrazine obtained above in Example 46 with 2 molar equivalents of acetic anhydride and then adding a small amount of sodium acetate as a catalyst, there can be obtained 1-acetyl-2-(3-acetoxy-S-butanesulfonamidobenzoyl)hydrazine.

Example 77 .1-ot-chlr0acetyl-2-(3 or chloroacetylamina-S-methaneswlfonamidobenzoyl)hydrazine (I; R is CH R is H, n is 1, Y is OlCI-I CO, Q is 3-ClCH CONH, Q is H).

By reacting (3-amino-5-methanesulfonamidobenzoyi) hydrazine obtained above in Example 42 with 2 molar equivalents of chloroacetyl chloride in the presence of an acid-acceptor, for example pyridine, there can be obtained 1-a-chloroacet'y1-2-(3-a-chloroacetylamino methanesulfon amidobenzoyl) hydrazine.

Example 78 1-acetyl-2-(3-rrmin0 5 methanesulfonamidobenzoyl) hydrazine (I; R is CH R' is H, n is 1, Y is CHgCO', Q is 3-NH Q is H).

By reacting the (3-methanesulfonamido-S-nitrobenzoyi) hydrazine prepared above in Example 41 with acetic anhydride according to the manipulative procedure described above in Example 73, there can be obtained l-acetyl-Z- (3-methanesulfonamido-5-nitrobenzoy1)hydrazine. By reduoing the latter with ammonium sulfide in an appropriate organic solvent, for example ethanol, there can be obtained 1-acetyl-2-(3-amino 5 methanesuifonamidobenzoyl hydrazine.

l-acetyl-2-(3amino-5-methanesul fonamidobenzoyl)hydrazine can be reacted with hydrochloric acid, hydrobromic acid, hydriodic acid, nitric acid, sulfuric acid, phosphoric acid, acetic acid, citric acid, lactic acid, tartaric acid or quinic acid to give the hydrochloride, hydrobromide, hydriodide, nitrate, sulfate (or bisulfate), phosphate (or acid phosphate), acetate, citrate (or acid citrate), lactate, tartrate (or bitartrate) or quinate salts, respectively.

I claim:

1. A member of the group consisting of (A) a compound having the formula wherein n is an integer from 1 to 2, R is alkyl having from one to twenty carbon atoms, R is a member of the group consisting of hydrogen and lower-alky l, Y is a member of the group consisting of lower-alkanoyl and loweralkanoyl substituted on the a-carbon atom by a member of the group consisting of halogen, amino, and cyano, and Q and Q each is a member of the group consisting of: hydrogen; lower-alkyl; halogen hydroxy; lower-alkoxy; nitro; amino; cyano; lower-alkylmercapto; loweralkylsulfinyl; lower-a'lkylsulfonyl; lower-alkanoylamino; lower-alkanoylamino substituted on the a-carbon atom by a member of the group consisting of halogen and cyano; lovver-alkanoyl; lower-alkanoyl substituted on the a-carbon atom by a member of the group consisting of halogen and cyano; lower-alkanoyloxy; and lower-alkanoyloxy substituted on the a-carbon atom by a member of the group consisting of halogen and cyano, and (B) acid-addition salts thereof.

2. An acid-addition salt of a compound having the formula wherein R' is alkyl having from one to twenty carbon atoms. 7

3. An acid-addition salt of a compound having the formula Cl 0 NHNHz wherein R is alkyl having from one to twenty carbon atoms.

4. An acid-addition salt of a compound having the formula wherein R is alkyl having from one to twenty carbon atoms and Y is lower-alkanoyl containing from one to five carbon atoms.

5. A compound having the formula l @(NHSOzRM wherein R is alkyl having from one to twenty carbon atoms, and Y is lower-alkanoyl containing from one to five carbon atoms.

6. An acid-addition salt of a compound having the formula C ONHNH;

wherein R is alkyl having from one to twenty carbon atoms and R is lower-alkyl.

7. An acid-addition salt of (Z-butanesulfonamidobenzoyl hydrazine.

8. An acid-addition salt of (3-butanesulfonamidobenzoyl)hydrazine.

9. An acid-addition salt of (4-butanesulfonamidobenzoyl)hydrazin'e.

10. An acid-addition salt of (4-pentanesulfonamidobenzoyl)hydrazine.

11. An acid-addition salt of (4-butanesul fonamido-2- chlorobenzoyl hydrazine.

12. An acid-addition salt of (4-butanesulfonamido-2- hydroxybenzoyl)hydrazine.

13. An acid-addition salt of (4-butanesul fonamido-2- methoxybenzoyDhydr-azine.

14. An acid-addition salt of (4-butanesul fonamido-3- hydroxybenzoyl hydrazine.

15. An acid-addition salt of [3,5-bis(methanesulfonamido) benzoyl] hydrazine.

16. An acid-addition salt of [3,5-bis(butanesulfonamido benzoyl] hydrazine.

17. An acid-addition salt of 1-(4-butanesulfonamidobenzoyl) -2-acety1hydrazine.

18. An acid-addition salt of l-(4-butanesulfona1nid0- benzoyl) -2-aminoacetylhydrazine.

19. 1 (4-butanesul-fonamidobenzoyl)-2-dichloroacety1- hydrazine.

20. An acid-addition salt of [4- (-N-methylbutanesulfonamido) benzoy-l]hydrazine.

21. A process for preparing (4-butanesulfonamidobenzoyl)hydrazine which comprises reacting a loweralkyl 4-aminobenzoate ester with a butanesul-fonyl halide 2523 in the presence of an acid-acceptor and reacting the resulting lower-alkyl 4-butanesulfonamidobenzoate ester with hydrazine.

22. A process for preparing (4-pentanesul-fonamidobenzoyl)hydrazine which comprises reacting a loweralkyl 4-aminobenzoate ester with a pentanesulfonyl halide in the presence of an acid-acceptor and reacting the resulting lower-alkyl 4-pentanesulfonarnidobenzoate ester with hydrazine.

23. The process which comprises reacting with hydrazine a compound of the formula COOR" wherein R is a member of the group consisting of hydrogen and lower-.alkyl; R is lower-alkyd; R is alkyl of from one to twenty carbon atoms; Q and Q each is a member of the group consisting of: hydrogen, lower-alkyl, halogen, hydroxy, lower-alkoxy, nitro, amino, cyano, lower-alkylmercapto, lower-alkylsulfinyl, lower-alkylsulfonyl, loweralkanoylamino, lower-al-kanoylamino substituted on the a-earbon atom by a member of the group consisting of halogen and cyano, lower'alkanoyl, lower-alkanoyl sub stituted on the a-earbon atom by a member of the group consisting of halogen and cyano, lower-alkanoyloxy, and lower-alkanoyloxy substituted on the a-carbon atom by 24 a member of the group consisting of halogen and cyano; and n is an integer from one to two thereby producing a compound of the formula CONHNH;

wherein R, R, R", Q, Q, and n have the meanings given above.

References Cited in the file of this patent UNITED STATES PATENTS OTHER REFERENCES Beilstein; Handbuch der Organ. Chem, volume 14, page 362 (1931).

Beilstein; Handbuch der Organ. Chem, volume 14, 21rd supplement, page 230 (1951).

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION March 10, 1964 Patent No. 3, 124,610

Aubrey A. Larsen It is hereby certified that error appears in the above numbered patent requiring correction and that the said Letters Patent should read as corrected below.

Column 5, lines 36 and 37', for "2-methanesu1fonamide" read 2-methanesu1fonamido line 44, for "Q is H" read Q is H column 11, line 36, for "R is CH (CH read R is CH and CH (CH line 69, for "(3methanesulfon amidobenzoy1)hydrazine", in italics, read (2-n'1ethanesu1fonamidobenzoyl)hydrazine in'italics; column 12-, lines 15 and 16, for "sulface" read sulfate column 15, line 10, for "40 mg./kg./day" read 450 mg./kg./day line 60, after "hydrazine" insert hydrate column 17, line 23, for

"C, 10.23" read S, 10.23 column 18, line 71, for "about" read above Signed and sealed this 15th day of September 1964,,

(SEAL) A'ttest:

EDWARD J. BRENNER Commissioner of Patents 

1. A MEMBER OF THE GROUP CONSISTING OF (A) A COMPOUND HAVING THE FORMULA
 23. THE PROCESS WHICH COMPRISES REACTING WITH HYDRAZINE A COMPOUND OF THE FORMULA 